Mechanisms of growth failure in experimental
nephropathy
Yi
Zhuwen, Liu Jianhua
Lab. Of
pediatric Nephrology, The Second Hospital of Xiangya School of Medicine,
Changsha, China
Objective: To
investigate the effect of malnutrition, nephrosis itself and steroid
therapy in growth failure in doxorubicin-induced nephropathy.
Methods: Twenty-four
male SD rats were randomly divided into control, pair-fed,
doxorubicin-induced nephrotic (nephrotic) and dexamethasone- treated
nephrotic(des-treated) rats. Serum GH, Serum and urinary GHBP and IGF-1
IGFBPs were determined. IGFBP-3 proteolytic activity in serum and urine
were analysed by IGFBP-3 protease assay (PTA); IGF-1/IGFBPs mRNA expression
in liver and kidney were assessed. GHR and IGF-1R in liver and kidney were
assessed.
Results: The increased
of length were the fastest in control, the faster in pair-fed rats than in
nephrotic rats and the slowest in des-treated rats during experiment
(P<0.001). Liver GHR was reduced gradually in accordance to the order from
control, pair-fed and nephrotic to des-treated rats (P<0.001). In
contrast to control, serum IGF-1 was reduced in pair-fed and nephrotic rats
(P<0.005), further decrease was seen in des-treated rats compared with
nephrotic rats (P<0.001). Urinary IGF-1 excretion was increased in
nephrotic rats compared with control and pair-fed rats (P<0.001),
diminished in des-treated rats compared with in nephrotic rats
(P<0.001). In contrast to control, serum IGFBP-2, -3, -4 were reduced in
pair-fed rats (P<0.005), however, IGFBP-3 was further decreased excess
pair-fed rats (P<0.005). In the urine, IGFBP-3 can be only measured in
nephrotic rats. In contrast to control, urinary IGFBP-3 protease activity
was increased in nephrotic rats rather than pair-fed rats; and decreased in
des-treaed rats compared with nephrotic rats. Hepatic IGF-1A mRNA
expression was higher in pair-fed and nephrotic rats than in control
(P<0.05). In contrast to control, hepatic IGFBP-2 mRNA expression was
decreased in pair-fed rats (P<0.005), increased in nephrotic rats
(P<0.001); further decrease was proved in des-treated rats (P<0.001)
compared with nephrotic rats. In contrast to control, renal IGF-1A mRNA
expression was increased in pair-fed and nephrotic rats (P<0.001); in
contrast to pair-fed rats, however, it was decreased in nephrotic rats (P<0.001); further decrease
was also found in des-treasted rats compared with nephrotic rats (P<0.001).
Conclusion: In summary,
secondary malnutrition, nephrosis itself and steroid therapy are the causes
of growth failure in the nephrotic rats. Diminished IGF-1 synthesis in
liver and target tissue due to increased serum IGFBP-2 are the main
mechanism of growth failure in nephrotic rats.